Bone formation and resorption have been linked to mechanical loads or centuries. Current concerns include: post-menopausal osteoporosis, skeletal development, prognosis for orthopedic and dental implants, iatrogenic orthodontic root resorption, and long-term weightlessness. Mechanical influences on non-bone cells are now also under close scrutiny. A common unknown is the transduction mechanism of mechanical forces into cell responses. One study approach uses a stress analysis tool (Finite Element Method, FEM) to model a loaded bone. A component (stress, strain energy ...) of the calculated mechanical environment within the bone is then associated with the observed loss and/or gain of bone. This attack was used in a two-dimensional analysis of orthodontic bone response in rat molar alveolus. The proposed project is intended to expand, refine, and further validate that model by focusing on the initial PDL cell response to orthodontics. The departures and advantages of the unique orthodontic model relative to orthopedic approaches are: (1) the experimental forces, applied with orthodontic precision, are more controllable and a traumatic than forces applied to long-bones, (2) the same system (tooth-alveolar bone) can he exposed to very different loading conditions (tooth tipping, intrusion, extrusion, lateral translation, or axial rotation), and (3) the focus of the study includes the periodontal ligament, the soft tissue reservoir of bone forming precursor cells, not only the hard tissues themselves. This approach, combining histologic and engineering analyses, has yielded novel concepts. We determined that bone formation may be linked to the mechanical environment within the soft tissues of the PDL, while resorption may be associated with the environment within the bone itself. The obstacles attributable to the anatomic complexity (five roots) and small size of the rat molar can be overcome with the proposed development of new (orthodontic and engineering) models based on larger dog teeth. Thus, the aims of this interdisciplinary project are to: (1) establish a larger and simpler (relative to rat molar) dog tooth model for orthodontic movement, (2) calculate the corresponding mechanical environment with three-dimensional FEM stress analysis, and (3) statistically investigate the relationship between components (tension, shear, etc.) of the mechanical environment and the new experimental results. To do so, dog mandibular second premolars will be tipped distally for 24 hours. Elastics attached to bonded brackets on the buccal and lingual surfaces of the second and third premolars will provide the force. The distribution of PDL cells synthesizing DNA as a result of orthodontics will be determined with BrdU labels. We expect the distribution pattern of these labelled cells to be correlated with the FEM calculated distributions of certain mechanical components. This, of course, would be valuable information about the mechanical stimulus that may be associated with cell response. Future research would need to look at other (axial rotation, translation, intrusion, extrusion) tooth movements. That should be followed by similar studies of long-bone behavior, including the consideration of the mechanical environment within the periosteum.